Major Depressive Disorder (MDD) is the most common mental illness, with estimated lifetime prevalence of 25%2. In addition, MDD is the fourth leading cause of disability and premature death worldwide3. Importantly, research suggests that the one-year prevalence rates of depression are relatively low in childhood, but dramatically increase, as much as six-fold, from early to late adolescence6-7. These trends have led researchers to examine the developmental antecedents to depression in hopes of identifying risk factors associated with the first onset of disorder. In their review of the state f research on juvenile MDD, Kovacs and Lopez-Duran1 commented on the importance of understanding the multifaceted equifinality of early life experiences in the etiology and course of depression. This study proposes to examine the relationship between two empirically supported risk factors: stress reactivity and cognitive vulnerabilities (CV). To varying degrees, these factos have been examined throughout development~ yet, these bodies of literature have been surprisingly separate, which may contribute to the disappointing performance of selective intervention strategies to identify and treat youth at risk1. Importantly, an integrative approach s necessary to capture the complex association between individual risk, environmental influences, and their subsequent prediction of depressive outcomes. This study proposes a first step in understanding the relationship between CV and stress reactivity in a salient developmental time period and proposes to take advantage of an ongoing NIMH funded R01 grant that is targeted at understanding the development and course of depression from pre- adolescence through late-adolescence in a demographically diverse sample. The primary aims of the proposed study are to (1) examine the developmental antecedents of CV and stress reactivity, (2) evaluate the combined role of these two risk factors for depression, and (3) examine whether CV predicts stress reactivity. In addition, this study will explore whether stress reactivity mediates the relationship between CV and depression and whether gender and racial differences are evident in the effects of these risk factors. Because adolescence marks a period of dramatic increase in rates of depression, 7-8 this study proposes to include a racially diverse community sample of youth that have been assessed in an ongoing NIMH funded study and will be followed prospectively. At their next visit for the study, participants will complete measures of CV, life experiences and diagnostic interviews, and a psychosocial stress task whereby their biological (neuroendocrine and autonomic nervous) responses will be assessed. This study has the potential to provide a more complete understanding of developmental antecedents and risk factors involved in social stress reactivity, CV, and the development of MDD. Given the high prevalence and burden of MDD, research is needed to understand the causal factors at play in the development of MDD. Results from this study may help to improve prevention programs, early intervention strategies, and treatment outcomes among youth. PUBLIC HEALTH RELEVANCE: Major Depressive Disorder (MDD) is the most prevalent mental illness associated with a number of maladaptive outcomes for the individual and society as a whole. The proposed study is designed to examine the relationship between and combined effects of two known risk factors for the development and maintenance of MDD in adolescents, namely cognitive vulnerabilities and stress reactivity. These two factors, which support the framework for cognitive behavioral therapy, are important aspects of a programmatic examination necessary to improve prevention and early intervention programs, and treatment outcomes among youth.